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This morning, drug researchers and cardiologists were again shocked by a big "everything you thought you knew is wrong" moment.

Niacin, a B vitamin, has been used for forty years to help millions of patients control their cholesterol levels. A prescription form, Niaspan, has sales of $900 million a year for Abbott Laboratories' AbbVie unit. had hoped to have an even bigger success with a new version that combined niacin and another drug to reduce the vitamin's main side effect: making patients' faces flushed and hot.

When Merck first announced it was developing that drug, known as Tredaptive, in 2007, it hoped for a rapid approval. It got one in Europe. But the Food and Drug Administration demanded a bigger study of Merck's niacin combo, Tredaptive, before it would clear the medicine for sale.

The FDA was right. Today Merck announced the results of that study, led by independent researchers at Oxford University and involving 25,673 patients. The drug did not reduce heart attacks, strokes, deaths, or heart procedures. There was also a "serious adverse event" that occurred more frequently among those who took the medicine than among those who didn't. Merck has not disclosed what this side effect was, but says it will inform regulators and work with researchers. In the meantime, it took the unusual step of advising doctors in areas where Tredaptive is approved not to prescribe the drug to new patients.

The result is likely to dramatically reduce the use of niacin, already on the wane. It will also make it harder to get new heart drugs approved and to market medicines that are already for sale but are not backed by big studies confirming their benefits. Along with a string of heart drug failures, it could make investors doubt the prospects for cholesterol medicines in clinical trials, making it harder for drug companies to finance new research in heart disease.

This is the second time that niacin, long a mainstay of therapy, has failed to benefit patients in a large clinical trial. A study funded by the National Institutes of Health, called AIM-HIGH, also failed to show a benefit for Niaspan. Cardiologists say the result is likely to mean that the use of niacin will plummet.

"We've all been bombarded with the fiscal cliff. This is going to be the niacin cliff," says William Boden, Chief of Medicine at the Samuel S. Stratton VA Medical Center in Albany,, who led AIM-HIGH. "There's already been a decline in niacin usage. In all the lectures I've given physicians and practitioners are skeptical. I can spin the results to a degree, but the doctors say show me the evidence. What the doctors say is if HPS-Thrive is negative, we're bailing. There will be much less enthusiasm for prescribing niacin now."

Randy Thomas a preventative cardiologist at the in Rochester, Minn., says: "I don't think there will be much of a future for niacin." He is disenchanted with many cholesterol-lowering drugs. The big exception, he says, are statin medications like Lipitor, Crestor, Zocor, and Pravachol, most of which are now cheap and generic and have been shown to reduce heart attacks and deaths in big studies, and which are among the most commonly prescribed medicines.There is no doubt that these medicines have a big benefit for heart patients.

"As we delve into the statin therapy there are probably multiple reasons that the statins are so beneficial and lowering [cholesterol] may be just one of the reasons for benefits from statins. Anti-inflammatory effects may be another factor."

Until detailed data from the Merck study are released later this year, it's hard to make firm conclusions about exactly why Tredaptive failed. It could even be that niacin is effective, at least in some people, or that the unknown side effect occurred in a predictable way that would not mean the drug should never be given.

One possibility is that niacin works, but that the flush-blocker Merck paired it with undermined its efficacy. That drug, laropiprant, "was a complete unknown," says Allen Taylor of Georgetown University. Research by Garret Fitzgerald at the University of Pennsylvania, who had a decade ago warned about the potential heart risks of the arthritis drugs Vioxx and Celebrex, seemed to show such an effect was possible. Early Merck research may have raised similar issues, according to James Stein at the University of Wisconsin.